MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer.

Abstract

Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor-positive (HR+), HER2- metastatic breast cancer (MBC).Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR+/HER2- MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible. Abemaciclib 200 mg was administered orally on a continuous schedule every 12 hours until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was investigator-assessed objective response rate (ORR). Other endpoints included clinical benefit rate, progression-free survival (PFS), and overall survival (OS).Results: Patients (n = 132) had a median of 3 (range, 1-8) lines of prior systemic therapy in the metastatic setting, 90.2% had visceral disease, and 50.8% had ≥3 metastatic sites. At the 12-month final analysis, the primary objective of confirmed objective response rate was 19.7% (95% CI, 13.3-27.5; 15% not excluded); clinical benefit rate (CR+PR+SD≥6 months) was 42.4%, median progression-free survival was 6.0 months, and median overall survival was 17.7 months. The most common treatment-emergent AEs of any grade were diarrhea, fatigue, and nausea; discontinuations due to AEs were infrequent (7.6%).Conclusions: In this poor-prognosis, heavily pretreated population with refractory HR+/HER2- metastatic breast cancer, continuous dosing of single-agent abemaciciclib was well tolerated and exhibited promising clinical activity. Clin Cancer Res; 23(17); 5218-24. ©2017 AACR.

• Authors: Maura N Dickler, Sara M Tolaney, Hope S Rugo, Javier Cortés, Véronique Diéras, Debra Patt, Hans Wildiers, Clifford A Hudis, Joyce O'Shaughnessy, Esther Zamora, Denise A Yardley, Martin Frenzel, Andrew Koustenis, José Baselga
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 17 Pg. 5218-5224 (Sep 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28533223 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Aminopyridines
• Benzimidazoles
• abemaciclib
• ERBB2 protein, human
• Receptor, ErbB-2
• CDK4 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Adult
• Aged
• Aged, 80 and over
• Aminopyridines (administration & dosage, adverse effects)
• Benzimidazoles (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors, genetics)
• Cyclin-Dependent Kinase 6 (antagonists & inhibitors, genetics)
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (classification, pathology)
• Female
• Humans
• Middle Aged
• Neoplasm Metastasis
• Prognosis
• Receptor, ErbB-2 (genetics)
• Treatment Outcome